On the current trend toward the aging society, abnormal acceleration of bone resorption in a man advanced in years involves many of various senile diseases. In particular, senile osteoporosis is prominent and about to become a great social problem. When the present pharmacotherapy for this senile osteoporosis is viewed, it is conducted to administer (1) estrogen, (2) protein anabolic hormone, (3) calcitonin or (4) vitamin D. However, their effects are found only in improvement of subjective symptom, and hence there is no critical therapy under the circumstances.
On the other hand, it is considered that factors causing osteoporosis include two of calcification and decalcification, and abnormal decomposition of supporting tissue, collagen. However, the development of pharmaceutical agents by paying attention to the abnormal acceleration of collagen decomposition is only now under way. It is reported that this collagen decomposition is involved by a group of cathepsins which are certain kinds of cysteine proteases, and particularly cathepsin L among the group of cathepsins deeply involves the decomposition FEBS Letters, Vol. 269, No. 1, pp. 189-193 (1990), "Intracellular Proteolysis" (Tokyo Kagaku Dojin)!. It is also proposed to use a cysteine protease inhibitor as a substance, which inhibits decreases of calcium salts and collagen fibers at the same time, in treatment for absorptive osteopathy (Japanese Patent Application Laid-Open Nos. 284127/1988 and 218610/1990). As to compounds which inhibit cathepsin B and cathepsin L, epoxysuccinic acid derivatives are reported in, for example, European Patent Publication No. 655447A1. However, these compounds inhibit cathepsin L and cathepsin B at substantially the same inhibition coefficients, and does not selectively inhibit cathepsin L which is said to involve bone resorption.
It is therefore an object to provide a novel compound which inhibits cathepsin L and family enzymes thereof at a concentration lower than against other cathepsin groups and is useful as an agent for preventing and treating osteopathy such as osteoporosis or hypercalcemia.